SALSA MLPA P260 PALB2-RAD50-RAD51C-RAD51D probemix
Intended use: The SALSA MLPA probemix P260 PALB2-RAD50-RAD51C-RAD51D is an in vitro diagnostic (IVD)1 or a research use only (RUO) assay for the detection of deletions or duplications in the human PALB2, RAD51C, RAD51D and RAD50 genes, in order to determine increased susceptibility to cancer, including but not limited to breast and ovarian cancer. Deletions or duplications in PALB2 can also confirm a potential cause and clinical diagnosis for autosomal recessive Fanconi-Anemia type N. This product can also be used for molecular genetic testing of at-risk family members.
Of note, all exons of PALB2, RAD51C and RAD51D are covered, whereas not all exons of RAD50 are covered in this probemix.
This assay is for use with human DNA extracted from peripheral blood. Deletions or duplications detected with the P260 PALB2-RAD50-RAD51C-RAD51D probemix must be verified by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the aforementioned genes are point mutations, none of which are detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of these genes. This probemix is not intended to be used as a standalone assay for clinical decisions. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
1Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of this product description. In all other countries, the product is for Research Use Only (RUO).
Clinical background: PALB2, RAD50, RAD51C and RAD51D all play a role in DNA damage repair and a defect in one of these genes can lead to increased risk of tumour formation. For breast cancer, autosomal dominant mutations in the genes BRCA1 and BRCA2 are the most frequent cause, followed by mutations in PALB2, CHEK2 and ATM, though with a much lower frequency (Buys et al. 2017). Mutations in PALB2 may also increase the risk of developing pancreatic cancer, although the evidence is limited (see Table 1). When both PALB2 copies are defect, it can result in Fanconi-Anemia (FA) type N. FA is characterized by physical abnormalities (such as short stature or abnormal skin pigmentation), bone marrow failure and increased risk for malignancies. The incidence of FA in general is 1:160,000 of which type N comprises less than one percent of the cases. FA type N is associated with an unusually severe predisposition to paediatric malignancies (https://www.ncbi.nlm.nih.gov/books/NBK1401/).
Autosomal dominant mutations in RAD51C or RAD51D result in increased risk for cancer, in particular ovarian cancer (see Table 1). One article describes a homozygous RAD51C point mutation, causing FA-like disorder (FA-type O) (Vaz et al. 2010).
Autosomal dominant RAD50 mutations are linked to an increased risk to cancer, specifically breast cancer (see Table 1). Compound heterozygosity for two point mutations in RAD50 has been described, causing Nijmegen breakage syndrome-like disorder, though only one family is mentioned (Waltes et al. 2009).
Table 1. Overview of different types of cancer caused by mutations in PALB2, RAD51C, RAD51D and RAD50, and its relative risk of developing the cancer.
* including point mutations, indels, deletions/duplications. Percentage depends on the population tested, e.g. in BRCA1/2 mutation negative population percentage can be higher.
# PMID is PubMed unique identifier.
Probemix content: This SALSA MLPA probemix P260 PALB2-RAD50-RAD51C-RAD51D contains 50 probes with amplifications products between 130 and 500 nt (table 2 in product description), including 10 reference probes. At least one MLPA probe is present for each exon of PALB2, RAD51C and RAD51D. For RAD50 eight probes are divided over the gene, including the first and last exon. The identity of the genes detected by the reference probes is available online (www.mlpa.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment (see table in product description). More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mlpa.com.
Of note, all exons of PALB2, RAD51C and RAD51D are covered, whereas not all exons of RAD50 are covered in this probemix.
This assay is for use with human DNA extracted from peripheral blood. Deletions or duplications detected with the P260 PALB2-RAD50-RAD51C-RAD51D probemix must be verified by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the aforementioned genes are point mutations, none of which are detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of these genes. This probemix is not intended to be used as a standalone assay for clinical decisions. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
1Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of this product description. In all other countries, the product is for Research Use Only (RUO).
Clinical background: PALB2, RAD50, RAD51C and RAD51D all play a role in DNA damage repair and a defect in one of these genes can lead to increased risk of tumour formation. For breast cancer, autosomal dominant mutations in the genes BRCA1 and BRCA2 are the most frequent cause, followed by mutations in PALB2, CHEK2 and ATM, though with a much lower frequency (Buys et al. 2017). Mutations in PALB2 may also increase the risk of developing pancreatic cancer, although the evidence is limited (see Table 1). When both PALB2 copies are defect, it can result in Fanconi-Anemia (FA) type N. FA is characterized by physical abnormalities (such as short stature or abnormal skin pigmentation), bone marrow failure and increased risk for malignancies. The incidence of FA in general is 1:160,000 of which type N comprises less than one percent of the cases. FA type N is associated with an unusually severe predisposition to paediatric malignancies (https://www.ncbi.nlm.nih.gov/books/NBK1401/).
Autosomal dominant mutations in RAD51C or RAD51D result in increased risk for cancer, in particular ovarian cancer (see Table 1). One article describes a homozygous RAD51C point mutation, causing FA-like disorder (FA-type O) (Vaz et al. 2010).
Autosomal dominant RAD50 mutations are linked to an increased risk to cancer, specifically breast cancer (see Table 1). Compound heterozygosity for two point mutations in RAD50 has been described, causing Nijmegen breakage syndrome-like disorder, though only one family is mentioned (Waltes et al. 2009).
Table 1. Overview of different types of cancer caused by mutations in PALB2, RAD51C, RAD51D and RAD50, and its relative risk of developing the cancer.
# PMID is PubMed unique identifier.
Probemix content: This SALSA MLPA probemix P260 PALB2-RAD50-RAD51C-RAD51D contains 50 probes with amplifications products between 130 and 500 nt (table 2 in product description), including 10 reference probes. At least one MLPA probe is present for each exon of PALB2, RAD51C and RAD51D. For RAD50 eight probes are divided over the gene, including the first and last exon. The identity of the genes detected by the reference probes is available online (www.mlpa.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment (see table in product description). More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mlpa.com.